Epithelial Mesenchymal Transition and Cancer Stem Cell-Like Phenotypes Facilitate Chemoresistance in Recurrent Ovarian Cancer

被引:209
作者
Ahmed, N. [1 ,2 ,3 ,4 ]
Abubaker, K. [1 ,3 ]
Findlay, J. [1 ,2 ,4 ]
Quinn, M. [1 ,2 ]
机构
[1] Royal Womens Hosp, Womens Canc Res Ctr, Melbourne, Vic, Australia
[2] Univ Melbourne, Dept Obstet & Gynaecol, Melbourne, Vic 3010, Australia
[3] Univ Melbourne, Dept Surg, Melbourne, Vic 3010, Australia
[4] Prince Henrys Inst Med Res, Melbourne, Vic, Australia
基金
英国医学研究理事会;
关键词
Ovarian carcinoma; stem cell markers; EMT; migration; metastasis; differentiation; chemoresistance; recurrence; CARCINOMA ASCITES SPHEROIDS; PANCREATIC-CANCER; SURFACE EPITHELIUM; TUMOR PROGRESSION; SIDE POPULATION; TGF-BETA; INITIATING CELLS; BREAST CANCERS; E-CADHERIN; IDENTIFICATION;
D O I
10.2174/156800910791190175
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Overcoming intrinsic and acquired chemoresistance is the major challenge in treating ovarian cancer patients. Initially nearly 75% of ovarian cancer patients respond favourably to chemotherapy, but subsequently the majority gain acquired resistance resulting in recurrence, cancer dissemination and death. This review summarizes recent advances in our understanding of the cellular origin and the molecular mechanisms defining the basis of cancer initiation and malignant transformation with respect to epithelial-mesenchymal transition (EMT) of ovarian cancer cells. We discuss the critical role of EMT frequently encountered in different phases of ovarian cancer progression and its involvement in regulating cancer growth, survival, migration, invasion and drug resistance. Using a model ovarian cancer cell line we highlight the relationship between EMT and the 'migrating cancer stem (MCS) cell-like phenotype' in response to drug treatment, and relate how these processes can impact on chemoresistance and ultimately recurrence. We propose the molecular targeting of distinct 'EMT transformed cancer stem-like cells' and suggest ways that may improve the efficacy of current chemotherapeutic regimens much needed for the management of this disease.
引用
收藏
页码:268 / 278
页数:11
相关论文
共 90 条
[1]
Overexpression of αvβ6 integrin in serous epithelial ovarian cancer regulates extracellular matrix degradation via the plasminogen activation cascade [J].
Ahmed, N ;
Pansino, F ;
Clyde, R ;
Murthi, P ;
Quinn, MA ;
Rice, GE ;
Agrez, MV ;
Mok, S ;
Baker, MS .
CARCINOGENESIS, 2002, 23 (02) :237-244
[2]
Molecular pathways regulating EGF-induced epithelio-mesenchymal transition in human ovarian surface epithelium [J].
Ahmed, N ;
Maines-Bandiera, S ;
Quinn, MA ;
Unger, WG ;
Dedhar, S ;
Auersperg, N .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2006, 290 (06) :C1532-C1542
[3]
Epithelial-mesenchymal interconversions in normal ovarian surface epithelium and ovarian carcinomas: An exception to the norm [J].
Ahmed, Nuzhat ;
Thompson, Erik W. ;
Quinn, Michael A. .
JOURNAL OF CELLULAR PHYSIOLOGY, 2007, 213 (03) :581-588
[4]
Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients [J].
Aktas, Bahriye ;
Tewes, Mitra ;
Fehm, Tanja ;
Hauch, Siegfried ;
Kimmig, Rainer ;
Kasimir-Bauer, Sabine .
BREAST CANCER RESEARCH, 2009, 11 (04)
[5]
Prospective identification of tumorigenic breast cancer cells [J].
Al-Hajj, M ;
Wicha, MS ;
Benito-Hernandez, A ;
Morrison, SJ ;
Clarke, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :3983-3988
[6]
Molecular phenotyping of human ovarian cancer stem cells unravel the mechanisms for repair and chemo-resistance [J].
Alvero, Ayesha B. ;
Chen, Rui ;
Fu, Han-Hsuan ;
Montagna, Michele ;
Schwartz, Peter E. ;
Rutherford, Thomas ;
Silasi, Dan-Arin ;
Steffensen, Karina D. ;
Waldstrom, Marianne ;
Visintin, Irene ;
Mor, Gil .
CELL CYCLE, 2009, 8 (01) :158-166
[7]
Ovarian surface epithelium: Biology, endocrinology, and pathology [J].
Auersperg, N ;
Wong, AST ;
Choi, KC ;
Kang, SK ;
Leung, PCK .
ENDOCRINE REVIEWS, 2001, 22 (02) :255-288
[8]
Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer [J].
Bapat, SA ;
Mali, AM ;
Koppikar, CB ;
Kurrey, NK .
CANCER RESEARCH, 2005, 65 (08) :3025-3029
[9]
Cyclopamine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma [J].
Bar, Eli E. ;
Chaudhry, Aneeka ;
Lin, Alex ;
Fan, Xing ;
Schreck, Karisa ;
Matsui, William ;
Piccirillo, Sara ;
Vescovi, Angelo L. ;
DiMeco, Francesco ;
Olivi, Alessandro ;
Eberharta, Charles G. .
STEM CELLS, 2007, 25 (10) :2524-2533
[10]
Exploring the role of cancer stem cells in radioresistance [J].
Baumann, Michael ;
Krause, Mechthild ;
Hill, Richard .
NATURE REVIEWS CANCER, 2008, 8 (07) :545-554